Revision of the risk of secondary leukaemia after mitoxantrone in multiple sclerosis populations is required.

The objective in this paper is to compare the cumulative incidence and incidence density of therapy-related acute myeloid leukaemia in two cohorts of patients with multiple sclerosis treated with mitoxantrone, and with previously reported data in the literature. Six new cases of acute myeloid leukaemia were observed by prospectively following two Spanish series of 142 and 88 patients with worsening relapsing multiple sclerosis and secondary-progressive disease treated with mitoxantrone. A literature review shows 32 further cases of acute myeloid leukaemia reported, 65.6% of which are therapy-related acute promyelocytic leukaemia. Five cases in the cohorts fulfilled the diagnostic criteria for acute promyelocytic leukaemia, and one patient was diagnosed with pre-B-acute lymphoblastic leukaemia. Acute myeloid leukaemia latency after mitoxantrone discontinuation was 1 to 45 months. The accumulated incidence and incidence density was 2.82% and 0.62%, respectively, in the Valencian cohort, and 2.27% and 0.44% in the Catalonian cohort. In the only seven previously reported series, the accumulated incidence varied from 0.15% to 0.80%. The real incidence of acute myeloid leukaemia after mitoxantrone therapy in the multiple sclerosis population could be higher as evidenced by the growing number of cases reported. Haematological monitoring should continue for at least 5 years after the last dose of mitoxantrone. These data stress the necessity of re-evaluating this risk.

Interferon beta in secondary progressive multiple sclerosis : daily clinical practice.

BACKGROUND AND OBJECTIVE: Observational studies may provide additional information about the behaviour of different drugs in the post-marketing period. We present the data from a cohort of secondary progressive multiple sclerosis (SPMS) patients treated with interferon beta (IFNbeta-1b) at our MS clinic. METHODS: This was an independent, open-label, non-randomised, observational study. Within the period 1998 to 2005, all patients with SPMS who started therapy with IFNbeta-1b at our centre were studied. Each patient was included in a follow-up protocol collecting demographic and baseline clinical data. RESULTS: We studied 146 SPMS patients with a median follow-up of 60 months. Over the total study period, 62.2% of patients had confirmed progression. The analysis of the time to con- firmed progression showed that patients with two or more relapses in the 2 years before IFNbeta initiation, had a higher risk of disability increase than those patients with less than two relapses (p = 0.002). Multiple regression analysis showed disease activity in terms of relapses as the only factor to predict increase of disability during the follow-up period. A significant proportion of patients (36%) stopped treatment during the follow-up period. IFNbeta was safe, although some unexpected adverse events were observed. CONCLUSIONS: A higher disease activity before the beginning of treatment with IFNbeta in SPMS patients with a given EDSS rank could identify those with faster disability progression after treatment initiation.

Is optic neuritis more benign than other first attacks in multiple sclerosis?

Optic neuritis presentations are thought to have a better prognosis. The aim of our study was to compare conversion to multiple sclerosis on the different topographies of CISs. We prospectively evaluated 320 patients with CISs (123 with optic neuritis, 78 with brainstem syndromes, 89 with spinal cord syndromes, and 30 with other topographies) who were observed for a median of 39 months. Patients underwent brain MRI within 3 months of their first attack and again 12 months later. Conversion to multiple sclerosis determined either clinically or by MRI was evaluated according to topography. Baseline MRI was normal in 49.2% of patients with optic neuritis compared with 24% in brainstem syndromes, 24% in spinal cord syndromes, and 18.5% in other syndromes. Optic neuritis behaved differently from the other CISs for lower conversion to clinically definite multiple sclerosis and smaller proportion of patients fulfilling MRI dissemination in space, time, or both. Nevertheless, when only patients with abnormal cranial MRI results at baseline were selected, no differences for clinical or MRI conversion were found. Optic neuritis has a smaller risk for conversion to multiple sclerosis. Nevertheless, MRI at baseline, not CIS topography, appears to be the crucial issue at multiple sclerosis presentation.